The effects of melatonin on vascular function, oxidative stress and blood pressure reactivity during a high sodium diet

High sodium diets (HSD) can reduce the ability of the arteries to properly dilate (i.e., vascular dysfunction), partially due to increases in reactive oxygen species (ROS). HSD can also cause exaggerated increases in blood pressure (BP) during different physiological perturbations (BP reactivity). Vascular dysfunction and increased BP reactivity are directly related to future atherosclerosis and hypertension (HTN) development, respectively, and thus, to CVD mortality. Melatonin, a hormone synthesized mainly at night from the pineal gland, ameliorates ROS in healthy and clinical populations, enhances mechanisms underlying proper vascular function in in vitro studies and improves in vivo endothelial function. Limited literature indicates that melatonin inhibits the sympathetic system responses and increases parasympathetic system responses. OBJECTIVES: 1) Determine the effects of melatonin on vascular function after 10 days of HSD. 2) Determine the effects of melatonin on BP responses after 10 days of HSD. 3) Determine the effects of melatonin on ROS levels after 10 days of HSD. HYPOTHESES: 1) Melatonin supplementation will increase vascular function on HSD compared to HSD alone. 2) Melatonin supplementation will decrease BP reactivity during isometric handgrip exercise (IHG) and post-exercise ischemia (PEI), and cold pressor test (CPT) on HSD compared to HSD alone. 3) Melatonin supplementation will decrease ROS levels on HSD compared to HSD alone. METHODS: Healthy, non-hypertensive and non-obese young adults were recruited. Participants underwent a randomized cross-over study including a 10-day HSD (6,900mg sodium/d) and supplemented with 10 mg of melatonin (HSD+MEL) and a 10-day HSD (6,900 mg sodium/d) and supplemented with placebo (lactose) (HSD+PL). 24-h BP was measured with an ambulatory monitor on day 8 of each intervention. Vascular function was assessed at both the conduit artery level via brachial artery flow-mediated dilation (FMD) and at the microvascular level via near infrared spectroscopy during a vascular occlusion test (NIRS-VOT). BP reactivity was evaluated by examining beat-to-beat BP reactivity to IHG and PEI and CPT. ROS levels were determined as superoxide (O2-) concentration measured with electron paramagnetic resonance. RESULTS: Twenty-four participants (13M/11W, 27.0 ± 2.8 yrs., body mass index 23.8 ± 1.9 kg/m2, BP: 111/67 ± 8/7 mm Hg) participated in this study. There were no differences in 24-h mean arterial pressure (MAP) at the end of each intervention (HSD+PL: 83 ± 6 mm Hg; HSD+MEL: 82 ± 5 mm Hg; p=0.35). Melatonin supplementation decreased nighttime systolic BP (HSD+PL: 106 ± 12 mm Hg; HSD+MEL: 101 ± 9 mm Hg; p=0.02) and increased nighttime systolic dipping (HSD+PL: 13.3 ± 7.4 %; HSD+MEL: 16.2 ± 6.8 %; p=0.04) on the HSD compared to a HSD alone. Brachial artery FMD% (HSD+PL: 7.4 ± 3.7 %; HSD+MEL: 6.9 ± 3.6 %; p=0.50) and tissue oxygenation index (TSI) recovery slope (HSD+PL: 0.2 ± 0.06 %/s; HSD+MEL: 0.2 ± 0.08 %/s; p=0.75) were similar at the end of each intervention. Free radical molarity (HSD+PL: 7.8 x10-5 ± 4.1 x10-5 mol/L; HSD+MEL: 8.7 x10-5 ± 5.1 x10-5 mol/L; p=0.51) or free radical number (HSD+PL: 8.0 x1015 ± 4.4 x1015; HSD+MEL: 9.0 x1015 ± 4.9 x1015; p=0.47) were not different at the end of each intervention. BP responses to physiological perturbations was assessed. MAP delta change (HSD+PL: 27 ± 13 mm Hg; HSD+MEL: 26 ± 9 mm Hg; p=0.78) and MAP percent change to IHG (HSD+PL: 32 ± 16 %; HSD+MEL: 31 ± 11 %; p=0.80) were similar at the end of each intervention. MAP delta change (HSD+PL: 22 ± 10 mm Hg; HSD+MEL: 22 ± 9 mm Hg; p=0.96) and MAP percent change to PEI (HSD+PL: 26 ± 12 %; HSD+MEL: 27 ± 12 %; p=0.98) were also similar at the end of each intervention. Lastly, MAP delta change (HSD+PL: 23 ± 14 mm Hg; HSD+MEL: 22 ± 15 mm Hg; p=0.60) and MAP percent change to CPT (HSD+PL: 27 ± 17 %; HSD+MEL: 25 ± 17 %; p=0.47) were similar at the end of each intervention. CONCLUSION: Melatonin supplementation under a HSD did not improve vascular function, decrease free radicals levels or decrease BP responses to IHG, PEI or CPT under a HSD alone in this cohort of young healthy normotensive adults. Melatonin supplementation under a HSD decreased nighttime systolic BP and increased nighttime systolic dipping compared to a HSD alone.

Grantor dc:publisher

University of Delaware

Year dc:date.issued

2022

Author dc:creator

• Ramos Gonzalez, Macarena

• Blood pressure
• Blood pressure reactivity
• High sodium
• Melatonin
• Oxidative stress
• Vascular function

DOI

https://doi.org/10.58088/580s-rj75

OAI identifier oai:identifier

oai:udspace.udel.edu:19716/31520